I. Field
The present disclosure relates to the fields of molecular biology and medicine. More particularly, it relates to the fields of inflammation and inflammatory disease. Specifically, it deals with the use of antibody-siRNA conjugate to treat rheumatoid arthritis.
II. Related Art
Rheumatoid Arthritis (RA), an inflammatory autoimmune disease of the joints, affects approximately 0.24% of the world population (Cross et al., 2014). This number will rise as the population continues to age. Patients suffering from RA initially experience joint pain which often progresses to joint destruction ultimately leading to the crippling of the patient. It has been estimated that in the U.S., close to 800,000 adults are work-disabled due to this disease (Pincus et al., 1984; Sokka et al., 1999). While the advent of the Biological class of therapeutics has improved outcomes, many patients respond partially or not at all. Thus there is an urgent need for new therapeutics to treat RA.
It is well accepted that complement plays an important role in the development of RA (Ballanti et al., 2013). Of the several components of complement, current evidence points to the component C5 as the most important and strongest inducer of inflammation and the immune response (Woodruff et al., 2011). C5 is cleaved into C5a and C5b. C5a functions as a general activator of inflammatory cells via the C5a receptor (C5aR) while C5b promotes the assembly of the membrane attack complex (MAC, C5b-C9). Several groups generated antibodies or small molecule inhibitors against C5a and C5aR (CD88) which have showed some efficacy in RA in animal models. However, none of these candidate therapeutics have moved from bench to bedside. Therefore, improved clinical interventions in the complement pathway are needed to advance the treatment options for RA.